The Cardiac Benefit of Testosterone Replacement in Men With Low Testosterone Levels With Coronary Artery Disease After Successful Intervention of the Blockage or Narrowed Heart Artery

The Cardiac Benefit of Androgen Replacement in Hypogonadal Males With Coronary Artery Disease Following Successful Percutaneous Coronary Intervention (PCI).

The purpose of the study is to find out if giving the study drug, Androgel (testosterone) as a testosterone replacement help bring the testosterone to an acceptable level and to find out if it will help improve heart condition in males with coronary artery disease (CAD) following successful percutaneous coronary intervention.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: AndroGel 5 Grams; Drug: Placebo

Detailed Description

Males with coronary heart disease have lower serum levels of bioavailable testosterone than men of a similar age with normal coronary angiograms (English, European Heart Journal, 2000). Low plasma testosterone has been associated with known risk factors for CHD, including age, obesity, hyperinsulinemia, diabetes, and adverse lipid profile.

Testosterone has also been shown in numerous studies to be a vasodilator. Recently, testosterone replacement compared with placebo, in hypogonadal men was shown to improve time to ischemic threshold, assessed by treadmill exercise testing at 4 and 12 weeks (Malkin, Heart, 2000). Prior studies had also shown a beneficial effect on exercise-induced ischemia in men with CAD, but not exclusively hypogonadal men (Jaffe,Br Heart J 1977; Rosano, Circulation, 1999; English, Circulation, 2000). In addition, this proposed study would be the first study to assess if the anti-anginal effects persists long term.

This is a randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of testosterone supplementation in hypogonadal men with coronary artery disease following successful revascularization with percutaneous coronary intervention (PCI). Only those men who had successful coronary artery revascularization, and on stable cardiac medical regimen for the prior 4 weeks will be included. Eligible patients will then be randomized on a 2:1 basis with 50 subjects receiving 5 grams of AndroGel and 25 subjects receiving placebo gel.

The men in this study who demonstrate hypogonadism represent a novel population to demonstrate the safety and efficacy of testosterone supplementation to improve cardiac function and outcomes. We hypothesize that treatment of hypogonadism in men with CAD, following successful PCI, will significantly improve cardiac ischemic threshold as assessed by cardiac stress testing. Furthermore, additional cardiac endpoints such as angina status, endothelial function and inflammatory serum markers will also demonstrate significant benefit in the testosterone treated group.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Adult male patients with coronary artery disease (CAD) (one to three vessel diseased).
• Stable cardiac status at least 3 months after percutaneous coronary intervention (PCI).
• No change in cardiac medications for 4 weeks prior to enrollment.
• Testosterone < 300 ng/dl or free testosterone < 5.0 ng/dl or bioavailable testosterone < 150 ng/dl.
• Sex Hormone Binding Globulin (SHBG) < 7nmol/liter and Free Testosterone < 50pg/dl
• Prostate Specific Antigen (PSA) < 2.5 ng/mL or 2.6-3.7ng/mL with a negative prostate biopsy within the last 6 months and pathology report available for investigator's review.
• Subgroup of diabetics with well to moderately controlled diabetes (defined by a HgbA1c of < 9mg/dL.

Exclusion Criteria:

• Hematocrit greater than 50%.
• Severe hypertension (exhibit systolic blood pressure >180mmHg and diastolic blood pressure >110 mmHg at baseline visit or a have a history of malignant hypertension.
• Significant cardiac arrhythmia (supraventricular tachycardia [SVT] or ventricular tachycardia with heart rate exceeding 110 beats per minute at Visit 1).
• ECG abnormalities precluding ST segment analysis on treadmill, or inability to walk on treadmill.
• Poorly controlled, symptomatic, active medical problems (HIV, hepatitis, cancer, benign prostatic hypertrophy, alcohol or drug abuse, major depressive disorder).
• Neurological or psychiatric disorder that would compromise the patient's ability to give informed consent or adhere to the requirements of the protocol.
• History of prostate cancer
• History of hypersensitivity to transdermal testosterone gel.
• International Prostate Symptom Score (IPSS) >19 at Visit 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Androgel treatment; Androgel 5 grams Androgel treatment - subjects will be instructed to begin the study drug at 1 week post entry into the study and will continue to take the study drug for a total of 6 months. The study drug has to be applied to the skin once daily for 6 months.	Drug: AndroGel 5 Grams; Placebo (randomization will occur on a 2:1 drug to placebo). A total of 50 subjects will be randomized to receive Androgel 5 grams and 25 subjects will be randomized to receive placebo. Androgel treatment/Placebo (after the treatment arm is assigned, subjects will be instructed to begin the study drug at 1 week post entry into the study and will continue to take the study drug for a total of 6 months. The study drug has to be applied to the skin once daily for 6 months.
Placebo Comparator: Placebo; Placebo - will be instructed to begin the study drug at 1 week post entry into the study and will continue to take the study drug for a total of 6 months. The study drug has to be applied to the skin once daily for 6 months.	Drug: Placebo; Placebo (randomization will occur on a 2:1 drug to placebo). A total of 50 subjects will be randomized to receive Androgel 5 grams and 25 subjects will be randomized to receive placebo. Androgel treatment/Placebo (after the treatment arm is assigned, subjects will be instructed to begin the study drug at 1 week post entry into the study and will continue to take the study drug for a total of 6 months. The study drug has to be applied to the skin once daily for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Stress Test: Time to ST Depression	Treadmill exercise testing performed according to the Bruce protocol (MAX-1 Marquette advanced exercise system, software version 002E). The system analyzed the signal averaged ECG and produces a graphical display of the level of the ST segment 80 ms after the J point against time. Time to 1 mm ST depression was measured from computer derived analysis, effectively eliminating observer bias.	at 6 months
Cardiac Stress Testing: Exercise Capacity	Exercise capacity was measured using exercise time.	At 1 month, 3 months, and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seattle Angina Questionnaire (SAQ)	A cardiac disease-related quality-of-life measure. The SAQ is a self-report instrument with 19 items that, yields five subscale scores: physical limitation, angina stability, angina frequency, treatment satisfaction, and disease perception. The possible range of scores for each of the five subscales is 0 to 100, with higher scores indicating better quality of life. A change of 10 points in any of the subscales is considered to be clinically important. Data not collected.	up to 6 months
Reactive Hyperemia Index	The Reactive Hyperemia Index measures the endothelial function and predicts future coronary events. In general RHI values below 2 are categorized as endothelial dysfunction and have a greater plaque burden, whereas higher RHI values are considered normal or improved endothelial function. PAT is the technique to non-invasively assess endothelial function. It comprises finger probes to evaluate digital volume changes.	6 months
International Prostate Symptom Score (IPSS)	IPSS has 7 questions related to symptoms, each item scored 1-5. Total score can range from 0 to 35 (asymptomatic to very symptomatic). The 8th question refers to the patient's perceived quality of life ranged from 0 to 6 ("delighted" to "terrible".) Data not collected.	6 months
Metabolic Equivalents of Task (METS)	The Metabolic Equivalent of Task (MET), or simply metabolic equivalent, is a physiological measure expressing the energy cost of physical activities and is defined as the ratio of metabolic rate (and therefore the rate of energy consumption) during a specific physical activity to a reference metabolic rate, set by convention to 3.5 ml O2·kg-1·min-1 or equivalently	6 months
Aging Male Symptoms (AMS)	The scale assesses symptoms of aging and their impact on HRQoL in males, and increases with increasing severity (1 to 5) of subjectively perceived complaints in 17 items. Scale ranges from 17-85 (no symptoms to extremely severe symptoms.)	At baseline, 1 month, 3 months, and 6 months
International Index of Erectile Function (IIEF)	Questions 1-5 15 of the IIEF relates to erectile function scale 0 - 30 (severe erectile dysfunction to no erectile dysfunction).	At baseline, 1 month, 3 months, and 6 months
IIEF-II Orgasmic Function	Questions 9-10 of the IIEF relates to orgasmic function scale 0 - 10 (from no impairment to severe impairment)	At baseline, 1 month, 3 months, and 6 months
IIEF -III: Sexual Desire	Questions 11-12 of the IIEF relates to sexual desire scale 0-10 (from very low to very high)	At baseline, 1 month, 3 months, and 6 months
IIEF-IV: Intercourse Satisfaction	Questions 6,7, 8 of the IIEF relates to intercourse satisfaction scale 0 - 15 (from very dissatisfied to very satisfied)	At baseline, 1 month, 3 months, and 6 months
IIEF-V: Over-all Satisfaction	Questions 13,14 of the IIEF relates to specifically to overall satisfaction scale from 0 - 10 (very dissatisfied to very satisfied)	At baseline, 1 month, 3 months, and 6 months

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Abbott
• Investigators: Principal Investigator: Mary Ann McLaughlin, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: December 18, 2006
• First Submitted That Met QC Criteria: December 18, 2006
• First Posted (Estimate): December 19, 2006

Study Record Updates

• Last Update Posted (Estimate): January 5, 2017
• Last Update Submitted That Met QC Criteria: November 7, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: coronary artery disease; percutaneous coronary intervention (PCI); Hypogonadal
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: GCO 06-1081